Elimination of mutant SWI/SNF complexes by protein quality control: new opportunities targeting aggressive rhabdoid tumours,Signal Transduction and Targeted Therapy

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Elimination of mutant SWI/SNF complexes by protein quality control: new opportunities targeting aggressive rhabdoid tumours
Signal Transduction and Targeted Therapy ( IF 40.8 ) Pub Date : 2024-09-06 , DOI: 10.1038/s41392-024-01935-9
Andreas Krämer _{1,

2,

3} , Stefan Knapp _{1,

2,

3}

Affiliation

A recent study published in Nature by Radko-Juettner and colleagues reports an unexpected mutant-specific synthetic lethality in which the E3 protein ubiquitin ligase DCAF5 specifically degrades mutant but not wild-type SWI/SNF chromatin remodeling complexes.¹ DCAF5 contains a likely druggable WDR domain, providing a new avenue for the development of novel therapeutics for aggressive cancers with SMARCB1 loss of function mutations.

中文翻译：

通过蛋白质质量控制消除突变 SWI/SNF 复合物：针对侵袭性横纹肌瘤的新机会

Radko-Juettner 及其同事最近在《自然》杂志上发表的一项研究报告了一种意想不到的突变体特异性合成致死性，其中 E3 蛋白泛素连接酶 DCAF5 特异性降解突变体而非野生型 SWI/SNF 染色质重塑复合物。 ¹ DCAF5 包含一个可能可药物化的 WDR 结构域，为开发针对 SMARCB1 功能缺失突变的侵袭性癌症的新型疗法提供了新途径。

更新日期：2024-09-06

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